Summary of Work: The early intervention studies explore how psychosis and early intervention might affect the course of schizophrenia, and how our understanding of that mechanism might lead to better treatments for patients. *THE NATIONAL COLLABORATIVE STUDY OF EARLY PSYCHOSIS AND SUICIDE (NCSEPS) Foremost among these studies is the National Collaborative Study of Early Psychosis and Suicide (NCSEPS), conducted in conjunction with the Department of Defense (DoD) and the Department of Veterans Affairs (VA). The NCSEPS population is active duty personnel hospitalized for either bipolar disorder, major depressive disorder, or schizophrenia while in the military, as well as a set of matched controls. The goals of the NCSEPS are: 1) to assess the characteristics of this first-episode population; 2) to determine rates of illness of these disorders in this population; 3) to detect and decrease the occurrence of long-term morbidity associated with these disorders; 4) to determine what benefits result from early intervention in patients first manifesting signs of these disorders; and 5) to decrease the risk of suicide in this population. The Armed Forces provide an excellent opportunity to study the potential benefits of early intervention in the major psychoses. Historically, a number of articles published over the course of this century indicate that a high percentage of individuals who become psychotic while in the military do so early in the course of their military career. Furthermore, there are a number of potential advantages to carrying out such a project within the DoD:. the highest risk period for developing schizophrenia and bipolar disorder occurs in the age range when most individuals enter the Armed Forces; the controlled environment individuals experience in the Armed Forces provides an almost unique opportunity to provide help; and studying servicemen and servicewomen provides the potential to follow-up those individuals who develop an illness through the VA. To date, NCSEPS has amassed sociodemographic characteristics and hospitalization data for over 15,000 patients and over 100,000 controls. Although analyses of these data are ongoing, a number of interesting preliminary findings have emerged. HOSPITALIZATION DURING THE FIRST 15 DAYS OF ACTIVE DUTY. The percentage of patients hospitalized within the first year of active duty who were also hospitalized within the first 15 days was 40.1% of those with bipolar disorder, 14.3% percent of those with major depressive disorder, and 37.3% percent of those with schizophrenia. All 3 patient groups had a high risk of hospitalization during the first 15 days of active duty, although the risk was much greater for bipolar disorder and schizophrenia. In order to assess the likelihood of pre-existing illness, with colleagues at Walter Reed Army Medical Center (WRAMC) we reviewed charts for 69 individuals in this sample hospitalized at WRAMC while on active duty. Data gathered included evidence of a prior suicide attempt, having psychiatric hospitalizations prior to beginning active duty, having a history of physical or sexual abuse, or having a history of any substance (alcohol or drug) abuse. Almost exactly half of the sample had at least one of the pre-existing conditions. No one in the "Other" category had been hospitalized before military service, but 33% of those with bipolar disorder, 13% of those with major depressive disorder, and 26% of those with schizophrenia had. Overall, 16% of the patients studied had a prior psychiatric hospitalization, and almost all of these were for mental health reasons rather than substance use. Though it appears high, this number implies that less than a fifth of the sample was previously hospitalized for an overt psychiatric condition. SOCIOECONOMIC STATUS (SES) FOR NCSEPS PATIENTS. In the NCSEPS study group, blacks received a diagnosis of schizophrenia more often than whites. This ethnic difference has been found in other studies of schizophrenia. To examine whether SES might explain the higher than expected rate, median household income from the 1990 US Census for each recruit?s home zip code was determined. Black schizophrenics were found to be from the poorest subgroup in the NCSEPS population, but the median income for all blacks surveyed by the 1990 Census was considerably lower. This suggests that another factor besides SES is at work. PRELIMINARY RESULTS FROM THE NATIONAL DEATH INDEX (NDI). The National Death Index (NDI) is a central, computerized database of mortality and cause of death information for the US. We requested information for 7875 patients and 3500 controls. We found a preliminary rate of 9 per 10,000 person years for all causes of death among the controls, and about 5 per 10,000 person years for suicide among the controls. In contrast, patients had a rate of 43 per 10,000 person years for all causes of death, and a suicide rate of 26 per 10,000 person years. USE OF VA SERVICES BY NCSEPS SAMPLE. 3378 treatment-eligible individuals hospitalized in the DoD between 1992 and 1996 were followed through to the VA. By September 1998, 52.5% of the sample had received outpatient care in VA mental health clinics. This rate of contact was lower than virtually all other studies of aftercare following inpatient discharge. Most contacts occurred in the first few months after DoD discharge. Individuals with a diagnosis of schizophrenia or bipolar disorder were more likely to seek VA outpatient care. Older individuals and individuals with more education were also more likely to seek care. Women and minorities were as likely as men to use these services. The NCSEPS project is particularly important because of its ability to follow a large number of patients before the onset of their illness through the VA system, and because of the availability of substantial amounts of pre- and post-morbid data. *MEDICATION DISCONTINUATION AND RELAPSE IN SCHIZOPHRENIA In 1999, NPB researchers published a study that looked at medication discontinuation in over 100 patients with chronic schizophrenia placed on an experimental protocol involving a placebo period of at least 7 days. That study found that, by discharge, patients' rating scores on the Psychiatric Symptom Assessment Scale (PSAS) (a BPRS-like rating scale) had returned to baseline. When the 6-week response of placebo patients to the restoration of antipsychotic medications was studied, it was found that the speed with which patients recovered was highly variable. A second study (van de Laar et al, in press) looked at specific adverse events that occurred before, during, and after patients' placebo period. The study group was a subgroup of 55 patients from the original sample. The frequency and severity of adverse events experienced during their hospitalization by inpatients with chronic schizophrenia who had a placebo phase were modest. Only 36 out of 55 (65%) patients experienced an adverse event. The study found that most patients (82%) had no significant increase in adverse events during the placebo phase. One subgroup, however--patients who were discharged from the hospital within 2 months of resuming medications--had a significant increase in adverse events during the placebo phase, and this increase remained statistically elevated at discharge. The data suggest a correlation between the patients discharged earliest, at a time when recovery from placebo was underway but still highly variable, and those with the greatest increase in event scores. This finding suggests the importance of identifying these patients in advance (for instance at baseline), so the decision of whether or not to enter a placebo phase can be carefully weighed. In our analysis, unfortunately, these patients had no distinguishing characteristics at baseline.